N-phosphono-phosphatoalkyl cyclic amines



Patented Aug. 7, 1945 UNITED STATES PATENT OFFICEN-PHOSPHONO-PHOSPHATOALKYL CYCLIC ALIINES James G. McNally and Joseph B.Dickey, Rochester, N. Y., assignors to Eastman Kodak Company, Rochester,N. Y., a corporation of New Jersey No Drawing. Application June 26,1943,

Serial N 0. 492,445

8 Claims. (Cl.260-461) This'invention relates toN-phosphono-phosphatoalkyl cyclic'amines and to a process for thepreparation thereof. I

It is known that. certain unsaturated compounds, such as cyclohexene,allyl alcohol or aniline, react with phosphorus in the presenceof oxygento give phosphorus derivatives which,

upon treatment with water, yield phosphinatophosphate compounds(Berichte 47, 2802-28 14, 1914).

We have now found that N-alkenyl cyclic amines react with phosphorus inthe presence of oxygen to give phosphorus derivatives' which,

, upon treatment with oxygen, in the presence of water, yieldN-phosphono-phosphatoalkyl cyclic amines. It is, accordingly, an objectof our invention to provide new N-phosphono-phosphatoalkyl cyclicamines. vide a process for preparing such amines. Other objects willbecome apparent hereinafter.

In accordance with our invention, we react a N-alkenyl cyclic amine withphosphorus in the presence of oxygen and then react the resultingproduct with oxygen and water. The products obtained by reacting theN-alkenyl cyclicamines which we employ in practicing our invention canbe represented by the following general formula:

wherein R represents a hydrocarbon alkylene group, R represents ahydrocarbon group and D represents the remainder of a cyclic amine. Whena N-alkenyl cyclic amine of theabove general formula is reacted withphosphorus in the presence of oxygen, a compound of the followinggeneral formula is produced:

wherein R, R and D have the values set forth above. When a compound ofthis second general formula is treated with water and oxygen, inaccordance with our invention, a N-phosphonophosphatoalkyl cyclic amineof the following general formula-is produced:

A further object is to pro wherein R, R and D have the above referred-tovalues.

It is believed that the manner of practicing our invention isillustrated by the following examples. These examples are not intendedto limit our invention.

Example 1.-'-N-methyl-N- ('y-phosphono-B ph0s-' phatopropyl) -anilineCHI Q 144 g. (1 mole) of N-methyl-N-allylaniline were dissolved inbenzene. To the solution were added 62 g. (2 moles) of yellowphosphorus. The mixture was placed in a pressure bottle and shaken withoxygen until 64 (2 moles) had been absorbed. This absorption of oxygenis usually complete in about 24 hours. The resultingwhite solid, havingthe formula:

CHrCH-CH:

definite melting point and could not be distilled.

Example 2.N- (n-butyl) -N-( -ph0s1 hono-,8- phosphatopropyl)'-m-toluidine 203 g. (1 mole) of N-(n-butYl) -N-allyl-m toluidine were dissolvedin 500 cc. of benzene and 62 g. (2 moles) of finely divided yellowphosphorus were placed in a pressure bottle and shaken under anoxygen-.-pressure of about two atmospheres until the gauge indicatedthat 64 g. (2 moles) of oxygen had been absorbed. About 24 hours usuallysuffices for this operation, The white solid thus obtained was separatedby filtration and added to 500 cc. of water. Air was passed into theaqueous mixture for 6 hours. The water was then removed from the mixtureunder reduced pressure. A colorless solid residue of N-(n-butyl) N ('yphosphono p phosphatopropyl) -m-toluidine was obtained. This compound isreadily hydrolyzed with dilute alkali or acid to N- (n-butyl) -N-('y-phosphono-p-hydroxypropyl) -m-toluidine, a colorless compound. Bothof these compounds are soluble in water, ethyl alcohol and dilute aceticacid. Neither compound has a definite melting point nor can bedistilled. The N- (n-butyl) -N'-allyl-m-toluidine employed in thisexample was prepared by condensing N-(n-butyl) -m-toluidine with allylchloride, in the presence of sodium carbonate.

235 g. (1 mole) of N-(p-hydroxyethyl) -N-crotyl-Z-methoxy-5-methylani1ine were dissolved in 500 cc. of benzene.To the solutionwere added 62 g. (2 moles) of yellow phosphorus. Themixture was placed in a pressure bottle and shaken with oxygen until 64g. (2 moles) had been absorbed. The absorption of oxygen is usuallycomplete in 24 hours. The resulting white solid was filtered off andadded to 500 cc. of water. Air was passed into the resulting mixture for6 hours. The water was then removed from the mixture under reducedpressure. 'A colorless solid residue of N- (,s-hydroxyethyl) -N-(v-phosphono-pphosphato-n-butyl) -2-methoxy-5-methylaniline remained.This compound can be readily hydrolyzed with dilute alkali or acid togive N-(phydroxyethyl) N-('y phosphono -fi hydroxy-nbutyl)-2-methoxy-5-methylaniline having the following formula:

This compound forms a stable salts with mineral acids and is soluble inethyl alcohol, acetic acid, dilute hydrochloric acid and water. TheN-(phydroxyethyl) N crotyl-2-methoxy- 5-methy1- aniline used in thisexample was prepared by condensing equimolecular amounts ofN-(p-hydroxyethyl) 2-methoxy 5 methylaniline and crotyl chloride, at thetemperature of a boiling water bath, in the presence of sodiumcarbonate. Upon washing the reaction mixture with water to remove saltsand distilling under reduced pressure, N s hydroxyethyl) N crotyl2-methoxy-5- methylaniline, boiling at 190 to 195 C. at 8 mm. of mercurypressure, was obtained. N- (p-hydroxyethyl) 2 methoxy 5-methylanilinewas prepared by condensing 2-methoxy-5-methy1 aniline with anequimolecular amount of ethylene oxide at 180 C. in an autoclave. Itboils at to C. at 10 mm. of mercury pressure. The term crotyl as used inthis entire specification is intended to mean the radical of theformula: -CH2-CH=CH-CH3.

Example 4.-N-('y-phosphono-fi-phosphatopropyl) -a-1z.aphthylamine 183 g.(1 mole) of N-allyl-a-naphthylamine were dissolved in 500 cc. ofbenzene. To the solution were added 62 g. (2 moles) of yellowphosphorus. The mixture was placed in a pressure bottle and shaken withoxygen under a pressure of 2 atmospheres until 64 g. (2 moles) had beenabsorbed. The absorption of oxygen is usually complete in about 24hours. The resulting white solid was filtered oil and placed in 500 cc.of water. Air was passed into the aqueous mixture for 6 hours. The waterwas removed from the mixture under reduced pressure. A colorless solidresidue of N-('y-phosphono-Bphosphatopropyl) a-naphthylamine remained.Upon hydrolysis with dilute mineral acid or alkaliN-(y-phosphono-p-hydroxypropyl) a-naphthylamine was formed, a colorlesscompound. Both of these compounds have indefinite melting points andcannot be distilled. They are soluble in alkalies, dilute mineral acids,ethyl alcohol, dilute acetic acid and 1,4-dioxane, TheN-allyl-a-naphthylamine used in this example was prepared by condensinga-naphthylamine with allyl chloride, in the presence of sodiumcarbonate. The slightly yellow compound boiled at to 198 C. at 18 mm. ofmercury pressure. Example 5.N ('y-hydroxypropyl) -N- -phosphono pphosphatop'ropyl)-3-acetamino-6- 252. go (1 mole) of N-( -hydroxypropyl)-N- allyl-3-acetamino-6-ethoxyaniline were dissolved CHaC ONE in 500 cclof benzene. To the solution were added 62 g. (2 moles) of yellowphosphorous. The mixture was placed in a pressure bottle and shaken withoxygen, under 2 atmospheres pressure, until .64 g. (2 moles) of oxygenwere absorbed. The

absorption of oxygen is usually complete in about 24 hours. Theresulting white solid reaction product was filtered off and placed in750 cc. of water. Air was passed in the resulting mixture for 6 hours.The water was removed under reduced pressure. A colorless residue of N-(-hydroxypropyl) -N- ('y-DhOSDhOHO-cphosphatopropyl)-3-acetamino-6-ethoxyaniline remained. The compoundwas hydrolyzed by warming on a steam bath with 5 per cent aqueous sodiumhydroxide. The sodium salt of N-(v-hydroxypropyl) -N-(v-phosphono-fl-hydroxypropyl) -3- acetamino-G-ethoxyaniline wasrecovered by removal of the water under reduced pressure. TheN-(y-hydroxypropyl) -N-allyl -3-acetamino -6- ethoxyaniline used in thisexample was prepared as follows: -hydroxypropyl chloride (1.25 moles)was added slowly with stirring at 130 C. to a mixture of 0.63 mole ofsodium carbonate and 1 mole of 3-acetamino-6-ethoxyaniline. Heating.andstirring at 130 C. was continued for 6 hours. At. the end of thistime 0.55 mole of sodium carbonate and 1.1 moles of allyl chloride wereadded with stirring and heating at 130 C. Heating at 130 C. wascontinued until no more carbon dioxide was evolved. The mixture was thencooled and water added to dissolve the salt. The water insoluble portionwas distilled under reduced pressure and N-(y-hydroxypropyD-N-allyl -3-acetamino -6- ethoxyaniline boiling at 270 to 275 C. at .5 to 5 mm. ofmercury was obtained.

Example 6.--N'-('y-keto-.n butyl) -N- (or-phosplwno-y-phosphato-Z-butyl)-2- (n-butorvy) -5- methylaniline sure bottle and shaken with oxygen.under two atmospheres pressure until 64 g. (2 moles) of oxygen wereabsorbed. The absorption of oxygen is usually complete in about 24hours. The

resulting white solid reaction product was filtered off and placed in750 cc. of water. Air was passed into the resulting mixture for 6 hours.The water was removed under reduced pressure. A colorless residue ofN-cetyl-N-(y-phosphonop-phosphatopropyl)-3-methylaniline remained.

The compound was hydrolyzed by dissolving in inch pressure, until 64 g.(2 moles) of oxygen were absorbed. The absorption of oxygen is usuallycomplete in about 24 hours. The white reaction product was filtered offand added to one literof water. Air was passed into the aqueous mixturefor 6 hours. The water was removed under reduced pressure leaving acolorless viscous mass of N-(y-keto-n-butyl)-N-(a-phosphono--y-phosphato-2-butyl)-2- (n-butoxy)-5- methylaniline, soluble in dilutealkali. The N-(y-keto-n-butyl) -N- (2-butenyl-1)-2-(n-butoxy)-5-methylaniline used in this example was prepared by condensing N-(--keto-n-butyl)-2- (n-butoxy)-5-methylaniline with a-methylallylchloride, in the presence of sodium carbonate. It boils at 250 to 255 C.at 0.25 mm. of mercury pressure. The N- (-y-keto-n-butyl) -2-(n-butoxy)-5-methylaniline was prepared by, mixing one mole of2-amino-4-methylphenylen-butyl ether with vinyl methyl ketone andallowing-the mixture to stand for 24 hours, followed by heating underreflux for 5 hours. The mixture is then steam distilled to removeunreacted 2- amino-4-methylphenyl-n-buty1 ether.

Example 7.N-cetyl-N- ('y-phosphono-phosphat opropyl) -3-methyl anilineCiaHza water with two molecular proportions of hydrochloric acid andheating the mixture to boiling for a short time. Upon cooling, thehydrochloric acid was neutralized and the N-cetyl-N-( -phosphono 3-hydroxypropyl)-3-methylaniline was, salted out, filtered off and dried.One molecular proportion of this hydroxy derivative was dissolved in twomolecular proportions of hydrochloric acid. To the resulting solutionwas added one molecular proportion of sodium nitrite. Upon making theresulting mixture alkaline with sodium carbonate. a nitroso derivativeseparated and this was filtered ofi and charged into a shaking autoclavewith 10g. of Raney nickel and 500 cc. of ethanol. The resulting mixturewas reduced with hydrogen at to C. When 2 molecular proportions ofhydrogen were absorbed, the autoclave was cooled and the productremoved. The reaction product was warmed on a steam bath with 2 litersof ethanol and then filtered to remove the nickel catalyst. Sufficient2-N-hydrochloric was added to neutralize the base in the alcoholicsolution. The alcohol was then removed under reduced pressure. Theremaining white product which was slightly soluble in hot water has thefollowing formula:

Example 8.-N-( y-phosphono B phosphatapropyl)-7-methyl-1,2,3,4-tetrahydroquinoline complete in about 24 hours. Theresulting white solid material was filtered off and added to 500 cc. ofwater. Air was passed into the resulting mixture for 6 hours. The waterwas then removed from the mixture under reduced pressure. A

colorless solid residue of N-(v-phosphono-sphosphatopropyb- 7-methyl-1,2,3,4-tetrahydroguinoline remained. Upon hydrolysis, as in Ex-I ample 7, N-( -phosphono-s-hydroxypropy1)-7-methyl-1,2,3,4-tetrahydroquinoline was obtained.

'quinoline was prepared by hydrogenating 7- methylquinoline at 110 C.for Raney nickel. It boiled at 140 C. at 20 mm. of mercury pressure.

Example 9.-N- -phosphono-,3-phosphatoprop yl) -2-methylbenzomorpholine1'73 g. (1 mole) of N-allyl-2-methylbenzomorpholine were dissolved in500 cc. of benzene. To

this solution were added 62 g. (2 moles) of yellow phosphorus. Themixture was placed in a pressure bottle and shaken with oxygen, under apresa sure of 45 pounds per square inch, until 64 g. (2 moles) of oxygenwere absorbed. The absorption of oxygen is usually complete in about 24hours. The resulting white solid material was filtered off and added to500 cc. of water. Air was passed into the resulting mixture for 6 hours.The water was then removed from the mixture under reduced pressure. Acolorless solid, water-soluble residue ofN-('y-phosphono-,B-phosphatopropyl) 'l-methylbenzomorpholine, having nodefinite melting point, remained. The N-allyl-2-methylbenzomorpholineused in this example was prepared by condensing one mole of2-methylbenzomorpholine with 1.1 moles of allyl chloride, in thepresence of 0.55 moles of sodium carbonate until no more carbon dioxidewas evolved. The product was washed with water and distilled underreduced pressure. N allyl 2 methylbenzomorpholine boils at 140 to 145 C.at 17 mm. of mercury pressure.

We have also found that alkenyl aryl ethers and alkenyl substitutedamides can be reacted with phosphorus and oxidized in a similar manner.The following examples will serve to illustrate these reactions.

Example 10.'y Phosphono-p-phosphatopropylm-dimethylaminophenyl ether1'77 g. (1 mole) of allyl m-dimethylaminophenyl ether were dissolved in500 cc. of benzene. To the resulting solution were added 62 g. (2 moles)of finely divided yellow phosphorus. The mixture into the aqueousmixture for from 5 to 6 hours. The water was then removed under reducedpressure leaving a colorless residue of 'y-phosphono-fi- "Heating at toC. was continued until all the allyl chloride had reacted. Them-dimethyf aminophenylallyl ether was extracted with benzene anddistilled under reduced pressure. It boiled at to C. at 10 mm. ofmercury pressure.

Example 11.N (e methoxyethyl) -N-(- -phosphono-p-phosphatopropylcarbamidomethyD- aniline 248 g. (1 mole) of N-(e-methoxyethyl)-N-allylcarbamidomethylaniline were dissolved in 500 cc. of benzene. Tothe resulting solution were added 62 g. (2 moles) of finely dividedyellow phosphorus. The mixture was placed in a pressure bottle andshaken with oxygen, under two atmospheres pressure, until 64 g. (2moles) of oxygen were absorbed. The required amount of oxygen is usuallyabsorbed in 24 hours. The resulting white solid material was filteredoff and added to 1500 cc. of water. Air was passed into the aqueousmixture for from 5 to 6 hours. The water was then removed under reducedpressure leaving a colorless residue of N-(e-methoxyethyl) -N-y-phosphono-p#-phosphatopropyl carbamidomethyl) aniline. The N (pmethoxyethyl) -N-allylcarbamidomethylaniline used in this example wasprepared as follows; one mole of methyl chloracetate was dissolved in1000 cc.

of ethanol. The solution was cooled to from -5" to 0 C. To the cooledsolution was added dropwise with stirring over a period of 5 hours, 1mole of allylamine, keeping the temperature below 0 C. After theallylamine had been added, 1 mole of sodium bicarbonate was addedfollowed by 1- mole of p-methoxyethylaniline. The mixture was slowlywarmed to 80 C. and kept at that temperature until no more carbondioxide was evolved. The mixture was then steam distilled to remove theethanol and any unchanged a-methoxyethylaniline or allylamine. TheN-(p-methoxyethyl) N-allyl carbamidomethylaniline was extracted from theaqueous residue with benzene. The methoxyethylaniline was prepared byheating at 220 C. for 24 hours, 1 gram-mole of aniline, 5 grams of Raneynickel catalyst and 1.5 moles of ethylene glycol monomethyl ether. Whencooled, the reaction product was fractionated and there was obtained,s-methoxyethylaniline boiling at 130 C. at 13 mm. of mercury pressure.

The term alcohol radical," in accordance with customary usage, isintended to mean an organic radical which corresponds to an alcohol andis derived therefrom by dropping the hydroxyl group, e. g. n-propyl isderived from npropyl alcohol by dropping the OH group, benzyl is derivedfrom benzyl alcohol by dropping the OH group, and tertiary butyl isderived by dropping the OH from tertiary butyl alcohol.

This application is a continuation-in-part of our copending applicationSerial No. 368,660, filed December 5, 1940.

What we claim as our invention and desire to be secured by LettersPatent of the United States is: a

1. A process for preparing a N-phosphonophosphato-alkyl aryl aminecomprising reacting a N-alkenyl aryl amine with phosphorus and oxygenand reacting the resulting reaction product with oxygen and water.

2. A process for preparing a N-phosphonophosphato-alkyl aryl aminecomprisinglreacting a N-alkenyl aryl amine of the following formula:

wherein R. represents a hydrocarbon alkylene group, R represents ahydrocarbon alkyl group, R." represents an alcohol radical and Drepresents a .monocyclic aryl group of the benzene series. withphosphorus and oxygen and reacting the resulting product with oxygen andwater.

3. A process for preparing a N-phosphonophosphato-alkyl aryl aminecomprising re'acting a N-alkenyl aryl amine of the following formula:

represents a monocyclic aryl nucleus of the wherein R" represents analcohol radical and D 4 benzene series, with phosphorus and oxygen andreacting the reacting product with oxygen to water.

4. A N-phosphono-phosphatoalkyl aryl amine of the following formula:

wherein R represents a hydrocarbon alkylene group, R represents ahydrocarbon alkyl group, R" represents an alcohol radical and Drepresents a monocyclic group of the benzene series.

5. A N-phosphono-phosphatoalkyl aryl amine of the following formula:

